According to the report issued by the National Commission on Diabetics in 1976, as many as 10 million Americans (close to 5 percent of the population) may have diabetes. Although the symptoms of diabetes can be controlled with insulin therapy, the ocular complications of the disease seem to be poorly related to this control (Duke-Elder, 1967). Consequently, the retinal vascular disease which results from diabetes (diabetic retinopathy) has become a major cause of blindness in the U.S. Ideally, vision changes should be detected prior to the development of retinopathy. Unfortunately, standard clinical measures of vision do not provide a clue to the precursor changes which ultimately result in a blood-retina barrier breakdown. Our research (EY 02271) has shown that many diabetics have loss of vision function prior to visual acuity loss even in the absence of retinopathy. In a group of 46 diabetic patients with clinically normal visual acuity, the earliest loss appears to involve the blue-sensitive cone mechanism; many of the diabetics also have a slowing of glare recovery, a reduced contrast sensitivity function, and a loss of low contrast letter acuity when compared to age-matched normals. The proposed research is designed to identify the probable retinal site of the loss and allow the development of even more sensitive measures of the natural vision history which may be used in the future to study the efficacy of treatment prior to retinopathy. Using psychophysical tests of vision and concomitant measures of fundus signs (color fundus photography and fluorescein angiography), the research proposed is directed to answer the following questions: 1. What is the retinal site of the reduced sensitivity of the blue-sensitive cone mechanism? 2. What is the nature of the anomaly of the blue-sensitive cone mechanism (spatial and temporal resolution, adaptation kinetics, receptor orientation)? 3. What is the natural vision history of the diabetic patient and how does it relate to blood chemistry, the onset of retinopathy and the subsequent loss of visual acuity?